title: Extracellular superoxide dismutase haplotypes are associated with acute lung injury and mortality.
abstract: BACKGROUND
  Extracellular superoxide dismutase (EC-SOD) is a potent antioxidant that plays an important role in controlling oxidant-mediated stress and inflammation. High levels of EC-SOD are found in the lung. Acute lung injury (ALI) frequently occurs in patients with infection, and levels of EC-SOD have been shown to modulate severity of lung injury in transgenic animal models of endotoxemia-induced ALI. An R213G single nucleotide polymorphism (SNP) has been shown to alter levels of EC-SOD and patient outcomes in chronic obstructive pulmonary disease (COPD) and ischemic heart disease.
  
  
  OBJECTIVE
  To determine genetic variation in the promoter and EC-SOD gene and to examine whether EC-SOD haplotype blocks are associated with clinical outcomes.
  
  
  METHODS
  We sequenced the EC-SOD promoter and gene to determine genetic variation and linkage disequilibrium (LD) patterns in a European American population. Two separate patient populations with infection-associated ALI were also evaluated to determine whether EC-SOD haplotypes were associated with clinical outcomes.
  
  
  RESULTS
  Sequencing resulted in the identification of 28 SNPs with relatively strong LD and 1 block consisting of 4691-5321-5360-5955-5982. This specific block was shown to be protective in two separate patient populations with infection associated ALI. In particular, patients with a GCCT haplotype had a reduced risk of time on the ventilator and mortality.
  
  
  CONCLUSIONS
  These results indicate that a GCCT haplotype may reduce inflammation in the lung, thereby decreasing the severity of lung injury and ultimately protecting patients from mortality associated with infection-induced ALI.
authors.affiliation: Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado at Denver, and Health Sciences Center, Denver, Colorado, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Arcaroli
authors.forename: John E
authors.initials: JE
authors.lastname: Hokanson
authors.forename: Edward
authors.initials: E
authors.lastname: Abraham
authors.forename: Mark
authors.initials: M
authors.lastname: Geraci
authors.forename: James R
authors.initials: JR
authors.lastname: Murphy
authors.forename: Russell P
authors.initials: RP
authors.lastname: Bowler
authors.forename: Charles A
authors.initials: CA
authors.lastname: Dinarello
authors.forename: Lori
authors.initials: L
authors.lastname: Silveira
authors.forename: Jeff
authors.initials: J
authors.lastname: Sankoff
authors.forename: Daren
authors.initials: D
authors.lastname: Heyland
authors.forename: Paul
authors.initials: P
authors.lastname: Wischmeyer
authors.forename: James D
authors.initials: JD
authors.lastname: Crapo
mesh_terms: D055371:Acute Lung Injury / Q000235:genetics* / Q000401:mortality*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D003120:Colorado / Q000453:epidemiology; D005260:Female; D014644:Genetic Variation; D015894:Genome, Human; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D013482:Superoxide Dismutase / Q000235:genetics*; D016019:Survival Analysis; D044465:White People / Q000706:statistics & numerical data
chemical_list: D015415:Biomarkers; C441642:SOD3 protein, human; D013482:Superoxide Dismutase